Ectopic hormone activity of primary and metastatic neoplastic lesions occasionally characterizes tumors of all types and is frequently detected in patients with lung carcinomas. Human chorionic gonadotropin (HCG) and adrenocorticotropic hormone (ACTH) are detected, respectively, in approximately 80% and 40% of all lung tumors examined, and HCG is found in nearly 100% of small cell lung carcinomas. Clinical analysis of ectopic hormones suggests their progressive appearance may signal cellular and behavioral changes in response to host or therapeutic influences on the course of paraneoplastic diseases. Ectopic hormones have been studied by histochemistry, immunocytochemistry, radioimmunoassay (RIA), and enzyme immunoassay (EIA). In this effort we are developing ultrasensitive enzyme radioimmunoassays (USERIA) for the more important ectopic hormones. We are currently studying ACTH, HCGB, prostaglandin G, and the unestablished calf thymus extract, thymosin alpha-1, recently thought to be associated with acquired immune deficiency syndrome (AIDS) and perhaps Kaposi's sarcoma.